Research needed on campylobacter vaccine for chickens

It is becoming increasingly clear that biosecurity measures on their own are insufficient for controlling campylobacter and that a vaccine is necessary before the industry can make significant strides in cutting its prevalence.

This has parallels with salmonella in eggs, where commercial launch of an effective vaccine greatly assisted in eliminating it from laying flocks. Vaccines have also proved successful in the control of various epizootic viral disease such as Newcastle Disease or infectious bursal disease (Gumboro).

The interest in reducing campylobacter is being driven by the European Commission which last year asked the European Food Safety Authority (EFSA) to consider approaches and targets to reduce campylobacter in poultrymeat. The poultry sector is being targeted as it has been suggested that up to 85% of human infections are caused by campylobacters from poultry.

Campylobacter jejuni and its close relative C coli commonly colonise the chicken gut in large numbers while the birds show no obvious symptoms. And these organisms contaminate carcasses during processing and can infect humans causing moderate-severe enteritis. Campylobacteriosis is now the most frequently reported cause of food poisoning in Europe.

Most intensively-reared flocks become campylobacter positive after two-three weeks of life (the lag-phase in colonisation). Studies have shown that transmission to flocks occurs horizontally from the environment via a number of routes including human traffic into the houses and possible vectors like water, rodents or flies.

Such routes could be minimised by strict biosecurity, but to date such levels of biosecurity have proved difficult to effectively introduce and maintain. Therefore, there is an increasing recognition for the need for complementary approaches, such as vaccination, to supplement biosecurity in protecting flocks from campylobacter colonisation.

Nevertheless to date, no effective campylobacter vaccines have been commercialised. To discuss progress in this area, an international scientific workshop was held back in April 2009 under the auspices of the European Network of Excellence, Med-Vet-Net.

Immunity to campylobacter

As early as 1992, it was reported that chickens infected with campylobacter generated detectable levels of antibodies in their blood and at the gut surfaces. These antibodies were directed against those parts of the bacterium essential for colonisation like the flagella (projections).

Importantly, the level of these antibodies was associated with the elimination of colonisation in older birds and with partial protection from subsequent challenges. Moreover, it appears that hens can transfer some of this protection, via antibodies in eggs, to their chicks and that this explains the observed lag-phase in flock colonisation. All this evidence provides considerable optimism that vaccination could generate protective antibody responses.

Antibodies are not the only way by which protective immunity is conferred. Certain cellular immune responses are also important in resistance to infection, especially during the initial stages of colonisation.

Recent studies have demonstrated that campylobacter stimulates these cellular responses and that they are genetically determined. This means that it may be feasible to breed future chickens that are more resistant against campylobacter.

Vaccination studies

Since the early 1990s, there have been many experimental studies on vaccination against campylobacter in chickens. Campylobacter is rarely, if ever, vertically transmitted so the target has to be the broiler not the parent flock.

In the broiler, the immune response has to be generated at the gut level, so the approaches used have either involved live organisms colonising the chicken’s gut and producing campylobacter antigens locally, or parts of campylobacter (so called sub-unit vaccines) delivered to the gut surface.

Currently two strategies are generating interesting results. The first strategy involves the use of a live salmonella vaccine genetically engineered to incorporate campylobacter antigens. The salmonella vaccine is also engineered to be quickly eliminated from the chicken’s gut, so that vaccinated birds would be salmonella-negative by slaughter.

To date these experiments have been undertaken using different salmonella strains and campylobacter antigens, by research groups in Poland and the USA. Both groups report successful protection against experimental challenge with campylobacter.

However, the use of a genetically engineered (GM) live salmonella vaccine in food production raises a number of issues regarding consumer acceptability and commercial viability, which will need to be addressed in Europe. Clearly considerable further research is needed to establish the effectiveness of this approach on commercial poultry units.

A second strategy, using sub-unit vaccines of campylobacter has been reported in the UK. Because this approach does not use GM vaccines, acceptability is not an issue. The problem with this approach is that such antigens, delivered orally, fail to generate a response at the chicken’s gut surface.

In mice and humans, there are several materials (adjuvants), which can effectively present the antigens to generate an immune response at the gut surface. Unfortunately, research has shown that most of these adjuvants are ineffective in the bird’s gut.

However, one such adjuvant, chitin microspheres, was able to effectively present a major campylobacter antigen, flagellin, to stimulate both antibody and cellular immune responses in chickens and that these responses gave protection against experimental challenge.

Both strategies provide proof that vaccination is a feasible way of protecting chickens from campylobacter. However, considerably more research is required to establish the practicality of such an approach on commercial units.

In particular there are practical issues regarding vaccine efficacy, safety and stability, as well the timing and delivery method to achieve protection in an immunologically immature and short-lived bird. There is also a need for fundamental research to select the best campylobacter antigens to use and the most suitable adjuvants or live vectors for delivery.

To conclude, vaccination is a long-term strategy requiring considerable future investment. But given the extent of the public health issue, the difficulty in excluding campylobacter from flocks and the current lack of an alternative strategy, a commitment to vaccine development may become worthwhile.

• Diane Newell is an independent consultant who established Food-borne Zoonoses Consultancy in September 2008. She previously worked for the Veterinary Laboratories Agency as a senior scientific consultant.